Outcome of COPD patients performing nocturnal non-invasive mechanical ventilation.

The role of non-invasive nocturnal domiciliary ventilation (NNV) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnia is still discussed. The aims of this study were to evaluate the long-term survival, the clinical effectiveness and side-effects of NNV in these patients. Forty-nine stable hypercapnic COPD patients on long-term oxygen therapy (LTOT) were assigned to two groups: in Group 1, 28 patients performed NNV by pressure support modality in addition to LTOT; in Group 2, 21 patients continued their usual LTOT regimen. Treatment was assigned according to the compliance to NNV, after an in hospital period. Mortality rate, hospital stay (HS) and ICU admissions (IA) were recorded in the two groups. HS and IA were compared to those recorded in a similar period of follow-back. Lung and respiratory muscle function, dyspnoea, and exercise capacity (by 6-min walk test) were evaluated baseline and every 3-6 months up to 3 yr. Mean follow-up time was 35 +/- 7 months. Mortality rate was not different between the two groups: 16, 33, 46% and 13, 28, 50% at 1, 2 and 3 yr in Groups 1 and 2 respectively. Lung and respiratory muscle function did not significantly change over time. A significant increase in 6-min walk test (from 245 +/- 78 to 250 +/- 88, 291 +/- 75, 284 +/- 89 m after 1, 2 and 3 yr respectively, P < 0.01) was observed only in patients undergoing NNV. In comparison to the follow back HS significantly decreased in both groups (from 37 +/- 29 to 15 +/- 12 and from 32 +/- 18 to 17 +/- 11 days/pt/yr in Groups 1 and 2 respectively, P < 0.001) whereas IA significantly decreased only in patients performing also NNV (from 1.0 +/- 0.7 to 0.2 +/- 0.3/pt/yr, P < 0.0001). Addition of NNV by pressure support modality to LTOT does not improve long term survival but significantly reduces ICU admissions and improves exercise capacity in severe COPD with hypercapnia.

Acute respiratory failure, due to severe obstructive sleep apnoea syndrome, managed with nasal positive pressure ventilation.

The complications of endotracheal intubation are particularly frequent in patients with obstructive sleep apnoea syndrome (OSAS). We prospectively tested nasal ventilation in such patients admitted for acute respiratory failure. Six consecutive patients, aged 17-70 yrs, were selected for the study. All patients were confused or severely obtunded, Glasgow Coma Score (GCS) 10 (SD 2). With nasal bi-level positive airways pressure (BiPAP) all these patients improved clinical status and arterial blood gas values, avoiding intubation and invasive mechanical ventilation. The median pH increased from 7.26 (SD 0.06) to 7.36 (0.01) and to 7.43 (0.02) after, 1-3 and 24 h of nasal ventilation, respectively. Nasal ventilation lasted an average of 21 (3) h on the first day. All patients were discharged home after a median hospital stay of 28 (11) days.

[The assessment of pulmonary arterial pressure by pulsed Doppler in patients with obstructive pneumopathy]. / Valutazione della pressione arteriosa polmonare mediante Doppler pulsato nei pazienti affetti da pneumopatia ostruttiva.

The severity of pulmonary arterial hypertension can be assessed by duplex-Doppler echocardiography, a subxiphoid approach and a general-purpose duplex device. Normally, the peak Doppler flow velocity occurs in midsystole and the flow profile is parabolic (bullet-like). In pulmonary arterial hypertension, changes in vascular compliance cause maximal acceleration of blood in early systole, with shortening of pulmonary acceleration time (AcT, or time to peak velocity). In the more severe cases, a midsystolic notching is visible, related to rapid deceleration of blood flow, followed by a brief secondary increase in velocity in the late systole. We studied 19 adult patients with chronic obstructive pulmonary disease with duplex-Doppler examination, with a subxiphoid approach and right heart catheterization. The study was diagnostic in all cases with Doppler recordings of good quality. An relationship was found between AcT and pulmonary mean or systolic arterial pressure at rest. An evident accurate prediction of pulmonary arterial pressure in emphysematous patients is possible by means of pulsed Doppler, also in case of low-level hypertension. We believe this method to be a simple and reliable adjunct to the non-invasive work-up of emphysematous patients and to represent a good alternative to the classical parasternal approach, which is often not feasible in these patients.

[Heart arrhythmias in chronic respiratory failure due to chronic obstructive bronchopneumopathy: the incidence and correlations with nocturnal respiratory disorders]. / Aritmie cardiache nella insufficienza respiratoria cronica da broncopneumopatia cronica ostruttiva: incidenza e correlazioni con le turbe respiratorie notturne.

The aim of this study was to assess: frequency and type of cardiac arrhythmias in patients with severe stable chronic obstructive lung disease (COLD) and chronic respiratory failure (CRF); diurnal or nocturnal predominance of the detected arrhythmias; prospective relationships between arrhythmias and nocturnal hypoxemic-hypercapnic episodes. All patients were examined with careful and complete medical history, chest roentgenogram, standard electrocardiogram, mono and bidimensional echocardiogram, respiratory function tests, arterial blood gases at rest, 24-hour dynamic electrocardiographic recording and, simultaneously, transcutaneous nocturnal monitoring of respiratory gases (TCNM). We studied 14 men: all complained of exercise-induced dyspnoea for 8 +/- 6 years; 10 of them reported usual nocturnal snoring. Respiratory function tests provided the following values (expressed in percentage compared with theoretical ones): vital capacity 58.6 +/- 15, forced expiratory volume/s 36 +/- 19, Tiffeneau index 60 +/- 19, Motley index 160 +/- 35, carbon monoxide diffusion capacity 48 +/- 26. Arterial blood gas analysis at rest resulted: PO2 47 +/- 4.5 mmHg, PCO2 49 +/- 7.9 mmHg, pH 7.38 +/- 0.3. Right ventricular diameter obtained with mono and bidimensional echocardiogram was 32 +/- 4.6 mm. Right pulmonary descending artery measured on chest roentgenogram was 23 +/- 3.8 mm. Nocturnal transcutaneous monitoring of respiratory gases showed mean PO2 of 40 +/- 9.7 mmHg and mean PCO2 of 75 +/- 19 mmHg. During night-time maximum percentage reductions of PO2 (36 +/- 17%) were measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Echoguided transvaginal oocyte retrieval: effective and easy to learn technique.

Echoguided transvaginal oocyte retrieval gives good results even when carried out after a short training course. This study compares the results obtained by a group of physicians with long experience and a newly-trained group. No significant differences were found in the percentages of follicles punctured (87.9% vs 91.9%), of oocytes recovered (62.8 vs 70.6%), in the mean number of follicles aspirated (4.5 vs 4.1) or in duration of the procedure (33.9 min vs 34.2 min). No complications occurred in the retrieval and the patients, pain was very slight.

Is pregnancy the best treatment for hyperprolactinaemia?

This paper reports the changes in prolactin levels after 12 spontaneous and 52 induced pregnancies in 54 women with unambiguous hyperprolactinaemia (median plasma prolactin levels 67.5 ng/ml, range 40-400). Twenty-three of the patients showed radiological evidence of prolactinoma. The pregnancies were induced in 37 patients by bromocriptine, in nine by metergoline, in two by lisuride and in four by other treatments. Of the 64 pregnancies, 16 ended in spontaneous abortion, while 48 went to term. Follow-up was continued for at least 6 months after delivery or until the end of lactation. In a control group of 32 hyperprolactinaemic women (median prolactin 70 ng/ml, range 40-400) not wishing to become pregnant, prolactin changes were similarly registered over a mean period of 15 months without any treatment (range 6-38 months). After pregnancy, a significant downward trend of plasma prolactin was observed in the puerperal women with a 'normalization' rate of 17%. No changes were observed in the 32 controls who did not become pregnant.

IVF: induction of ovulation in poor responders.

All IVF programs have a consistent rate of failure in inducing ovulations. Pharmacological induction of ovulation is otherwise crucial for an IVF program because of the need for more than one ovum. Since it is well known that the best candidates for HMG treatment are hypogonadotropic women a short reversible hypogonadotropic state was induced in IVF patients by LH-RH agonist (Buserelin). Superovulation was then achieved with very high initial doses of FSH (Metrodin) in order to maximize the ovarian response. This technique used in 116 IVF women induced a satisfactory follicle growth even in 70% of the patients already poorly responsive to HMG stimulation.

Ovarian stimulation of IVF patients: effects of the reversible hypogonadotrophic state induced by GnRH agonist.

Multiple ovulation was induced in 122 hypogonadotrophic IVF patients with large doses of HMG. The hypogonadotrophic state, short and reversible, was obtained by nasal administration of a GnRH agonist (200 micrograms, five times per day). In the 97 induced cycles, a mean of 9.1 follicles was recorded. A comparison of the results obtained for 36 patients who had already been treated with clomiphene and HMG showed both significantly more follicles per cycle (8.5 versus 3.0) and an increase in oocytes retrieved (6.7 versus 1.3) when treated with the agonist and HMG. In addition 11 of 18 already poorly responsive patients had normal responses. The luteal phase was supported by either HCG or progesterone injection. Plasma progesterone profiles were satisfactory and, as expected, the highest progesterone concentrations were associated with HCG treatment.

Spontaneous pregnancies in hyperprolactinemic women.

29 pregnancies occurred spontaneously in 28 women with mild to moderate hyperprolactinemia (prolactin levels up to 100 ng/ml). Only 4 of them showed tomographic evidence of microprolactinoma; 1 of the prolactinoma patients experienced a visual field defect at week 30, which was quickly controlled by bromocriptine treatment. Pregnancy was uneventful in the rest of the patients. Subjects who wished to lactate successfully breast-fed their babies. Of 22 women in whom prolactin levels were reevaluated at least 1 month after delivery and/or lactation, normal values were found in 9.

Effect of fenfluramine oral administration on serum prolactin levels in healthy and hyperprolactinemic women.

The effects of two different doses (40 and 80 mg orally) of fenfluramine on serum prolactin (PRL) levels have been evaluated in healthy and hyperprolactinemic women and compared with those of the potent dopamine antagonist sulpiride (100 mg i.m.). The lower fenfluramine dose resulted in a significant PRL rise in healthy women (n = 16) but not in hyperprolactinemics (n = 14). A dose-response effect was shown between 40 and 80 mg in control subjects (n = 7); in 4 hyperprolactinemics the higher dose also failed to increase PRL levels. Sulpiride resulted in a much greater PRL response. Since fenfluramine at the low doses used does not seem to exert antidopaminergic action, it is suggested that the mild PRL stimulation observed be mediated by the known brain serotoninergic activation induced by the drug.

Prolactin response to the dopamine antagonists sulpiride and domperidone. Further evidence for pituitary dopamine deficiency in hyperprolactinemic disorders of different etiology.

The PRL response to the dopamine antagonists sulpiride (100 mg i.m.) or domperidone (2 or 8 mg i.v.) was evaluated in healthy controls and in 148 patients with different hyperprolactinemic disorders (50 with idiopathic hyperprolactinemia, 58 with microprolactinoma, 19 with macroprolactinoma, 2 with empty sella, 8 with acromegaly, 7 with organic lesions of the hypothalamus, and 4 with idiopathic hypopituitarism of presumed hypothalamic origin). Mean PRL response to both drugs was significantly lower in all groups of patients than in controls, and significantly higher in subjects with idiopathic hyperprolactinemia than in those with pituitary adenomas or hypothalamic disease. Absent or impaired PRL responses were found in 38% of idiopathic patients, in 91.5% of microprolactinomas and in all of the patients with either macroprolactinoma, acromegaly, or hypothalamic disorders. Since the PRL response to dopamine antagonists depends on the presence of an endogenous dopaminergic tone, it is suggested that these figures reflect the incidence of major dopamine deficiency at pituitary lactotrophs in different hyperprolactinemic states. These data suggest that the pathophysiology of hyperprolactinemia in many patients with idiopathic disease is different from that of microprolactinoma. However, the finding of a normal PRL response to sulpiride in some subjects with radiologically or surgically proven microprolactinoma indicates that this test has no diagnostic value in the individual case.

Functional characterization of hypothalamic hyperprolactinemia.

PRL secretory dynamics were evaluated by several stimulation and suppression tests in nine patients with hyperprolactinemia due to organic hypothalamic disease. Basal PRL levels ranged between 20-63 ng/ml. There was a normal PRL response to TRH in eight cases (i.e. doubling of basal levels), whereas none of the seven tested subjects responded to sulpiride. The same dissociation of responses was not observed in any of the patients who were still hyperprolactinemic after surgery. Concomitant dopamine infusion resulted in sulpiride-induced PRL release in the four subjects so studied. None of 50 other hyperprolactinemic patients (11 with macroprolactinoma, 18 with microprolactinoma, and 21 with idiopathic hyperprolactinemia) showed PRL response to TRH but not to sulpiride. The TRH-induced PRL increase was significantly higher than that induced by sulpiride in hypothalamic hyperprolactinemia and significantly lower in idiopathic disease as well as in healthy controls; no differences were found in prolactinoma patients. The administration of substances resulting in stimulation of pituitary dopamine receptors, such as dopamine and L-dopa, induced a normal PRL suppression in 7 patients with hypothalamic disease so tested, whereas central nervous system-acting dopaminergic drugs, such as carbidopa plus L-dopa and nomifensine, failed to lower PRL levels in most cases (even when normoprolactinemic after surgery). These data suggest that the mild to moderate hyperprolactinemia found in many patients with hypothalamic lesions is due to dopamine deficiency at the pituitary level, that TRH and dopamine receptors at the lactotropes are intact in this condition, and that paired TRH and sulpiride tests may be of some diagnostic utility in hyperprolactinemic patients. They further suggest that subjects with so-called idiopathic hyperprolactinemia do not suffer from the type of hypothalamic derangement exhibited by patients with organic lesions of the hypothalamus.

Treatment of hyperprolactinemic states with different drugs: a study with bromocriptine, metergoline, and lisuride.

One hundred ninety-one hyperprolactinemic patients (78 women and 13 men; 54 with pituitary macroadenoma, 53 with microadenoma, and 84 with idiopathic disease) were treated for 2 to 48 months with one or two of the following prolactin (PRL)-lowering drugs: bromocriptine, metergoline, and lisuride. All of the three drugs used were highly effective in lowering PRL levels and restoring gonadal function both in females and in males in the majority of patients with either idiopathic or tumorous disease. In poorly responsive patients, increasing the drug doses resulted in further PRL lowering for all the three drugs. Mild side effects were frequently encountered with initiation of drug treatment but spontaneously subsided in most cases; severe side effects, necessitating stopping of the treatment, occurred in only 12 instances, but changing of the drug allowed PRL-lowering treatment to be continued in 11 of them.

Spontaneous and induced pregnancies in hyperprolactinemic women.

Sixty-nine pregnancies were observed in 57 hyperprolactinemic women (5 with pituitary macroadenoma, 20 with microadenoma, and 32 with normal tomography of the sella turcica). Ten of these pregnancies took place spontaneously in women with mild to moderate hyperprolactinemia (up to 70 ng/ml); 2 were induced by exogenous gonadotropins, 2 by clomiphene, 42 by bromocriptine, and 9 by metergoline; and 4 occurred after pituitary selective adenomectomy. The observed complications included spontaneous abortion (10 cases); headache (7 cases); sellar enlargement (5 cases); and bitemporal hemianopsia (1 subject with macroadenoma). Among 24 women in whom prolactin levels were reevaluated at least 1 month after parturition and/or lactation, 8 showed a decrease in prolactin concentration (less than 50% of pregestational levels), with actual prolactin normalization in 3 and resumption of cyclic menses in 2 previously amenorrheic women. In contrast, no changes in prolactin levels occurred after pregnancies that ended in abortion. These data suggest the following: 1) conception is not uncommon in women with moderate hyperprolactinemia; and 2) pregnancy may be safely induced without prior surgery and/or radiotherapy in hyperprolactinemic women, except those with large pituitary adenomas, and a considerable number of these patients even show a clinical and biochemical improvement after pregnancy.

Inhibition of luteinizing hormone release by dopamine infusion in healthy women and in various pathophysiological conditions.

To investigate the effect of dopaminergic stimulation on gonadotrophin release, serum LH and FSH concentrations were measured during dopamine infusion (5 microgram/kg/min for 120 min) in 8 healthy women in the early follicular phase, in 12 patients with hyperprolactinaemic amenorrhoea, in 5 subjects with premature ovarian failure and in 8 with polycystic ovarian disease and raised serum LH levels. Dopamine infusion produced a significant LH decrease compared with a control study using saline in all groups; there were no significant changes in FSH concentration. Between groups analysis showed a significantly greater LH fall in patients with polycystic ovarian disease than in the other groups. Dopamine inhibits LH release in healthy women and patients with anovulatory states of varying aetiology, and enhanced sensitivity to this inhibitory mechanism exists in polycystic ovarian disease. This finding suggests reduced dopamine activity at the median eminence level in this condition.